OVARIAN ACTIVIN RECEPTOR SUBTYPE AND FOLLISTATIN GENE-EXPRESSION IN RATS - RECIPROCAL REGULATION BY GONADOTROPINS

The production of activin, follistatin (FS), and inhibin, proteins pre sent in the ovary and involved in mammalian reproduction, is regulated by gonadotropins and estradiol. We report here gonadotropin regulatio n of ovarian activin receptor (ActR) subtype and FS mRNAs. Expression of ActRI, ActRIIA, ActRIIB, and FS mRNA was measured on the afternoon of proestrus (1800 h) and the morning of estrus (0800 h). ActRI and Ac tIIA subtype mRNA concentrations fell by similar to 50% (p < 0.05) fol lowing the proestrous gonadotropin surge (ActRIIB mRNA was undetectabl e), while FS mRNA was unchanged. To define the contribution of gonadot ropins, hypophysectomized (HYPOX) female rats were given recombinant h uman (rh) FSH and hCG, which decreased both ActR mRNAs (by similar to 70% and similar to 50% for ActRI and IIA, respectively) and increased FS mRNA by 2-fold. As gonadotropins could act via estradiol (E-2), HYP OX rats were given E-2; ActRI was decreased, but ActRIIA mRNA was incr eased. The actions of gonadotropins were preferential, as the combinat ion of rhFSH and hCG with E-2 reduced ActRIIA mRNA. FS mRNA was increa sed to a similar degree by E-2 and/or gonadotropins. These data sugges t that gonadotropins regulate ActR and FS gene expression via multiple mechanisms. Both a direct action on ActRIIA (inhibition) and an indir ect action through E-2 on ActRI (inhibition) and FS (stimulation) sugg est potential physiologic mechanisms for the reciprocal regulation of ActR subtype and FS mRNAs.